Month: June 2012

Concern about worse Leukemia outcomes in young adults

June 26, 2012 Chemotherapy, Hematology No comments , , ,

June 5, 2012 (Chicago, Illinois) — Cure rates of childhood leukemia are one of cancer’s best success stories, but when the disease strikes in adolescence or young adulthood, the outcomes are not quite as good.

This inferior outcome in adolescents and young adults (AYA), aged 16 to 30 years, has long been suspected from historic data, but it has now been confirmed by a major phase 3 trial. The new data, presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), shed light on why the outcomes are worse in this age group.

“The inferior outcome for AYA patients is the result of more resistant disease, resulting in higher rates of relapse and higher toxicity from treatment,” said lead author Eric Larsen, MD, medical director of the Maine Children’s Cancer Program in Scarborough.

“We have to find novel agents to better eradicate the leukemia,” he added.

Largest Cohort of this Age Group

This study, known as ALLL0232, was conducted by the Children’s Oncology Group and involved 2574 patients with acute lymphoblastic leukemia (ALL), 501 of whom (20%) were 16 to 30 years of age. “This is the largest cohort of this age group in a single cancer clinical trial,” Dr. Larsen noted.

The trial tested 2 treatment approaches. During the induction phase of treatment, the more potent steroid dexamethasone was compared with the standard prednisolone; during the interim maintenance phase of treatment, upfront high-dose methotrexate was compared with escalating intravenous methotrexate (Capizzi regimen).

The main results from this trial were reported at last year’s ASCO meeting, and have already had an impact on clinical practice. “We are already acting on the results from this trial,” said Jennifer McNeal, MD, assistant professor of pediatrics at the University of Chicago, Illinois, who moderated the session at which the updated results were reported.

Dr. McNeal said that her clinic has already switched to dexamethasone for younger patients with ALL, and that they are now using high-dose methotrexate instead of the Capizzi regimen in younger patients and in AYA.

Worse Outcomes

Results showing worse outcomes in AYA are cause for concern, Dr. McNeal said in an interview with Medscape Medical News. This is a patient population that has unique challenges, she explained. They appear to have a different biology, with a higher frequency of chromosomal abnormalities than children. There might also be compliance issue, she noted; once the young person is no longer under parental control, they might not adhere to clinic visits and medications. Many of the drugs that are used for maintenance are taken orally, and these young people might forget or decide not to continue taking the drug when they are feeling well, she added.

AYA had lower 5-year event-free survival than younger patients (68.0% vs 80.9%; P < .0001), and lower 5-year overall survival (79.8% vs 88.4%; P < .0001).

The 5-year cumulative incidence of relapse was higher for AYA than for younger patients (21.3% vs 13.4%), largely because of a higher rate of marrow relapses (15.2% vs 9.0%); the rate of central nervous system relapses was similar in the 2 groups.

In addition, fewer AYA than younger patients achieved remission (97.2% vs 98.8%; P = .013), and there were significantly more toxic deaths after induction and remission in AYA at 5 years (5.5% vs 2.1%; P < .0001).

Dr. Larsen said that these results have spurred the Children’s Oncology Group to consider a number of options to enhance leukemia control and reduce the toxicity of treatment.

Approached for outside comment, Eyal Attar, MD, assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital Cancer Center in Boston, said that the treatment outcomes of young adults with ALL have been an intense area of research in the past decade, with emphasis on why this age group fares better when patients are treated by pediatric oncologists using pediatric regimens than when they are treated by adult oncologists using adult-based regimens. It is possible that pediatric protocols tend to avoid myelotoxic drugs and that treatment compliance is aided by rigid protocols and patients’ mothers (the “mommy factor). Adult regimens tend to use more myelosuppressive agents, and patients treated by adult oncologists often have less parental involvement.

A separate question addressed by this study is why AYA do worse than younger children, he said. Because the same regimen was used in all ages in this study, the difference in outcomes must have another explanation. Specifically, this study shows that AYA have a lower remission frequency, higher toxic death rate, and decreased survival, relative to children. “These observations confirm what is believed about ALL and chemotherapy — that there are age-associated differences in the basic biology of the disease that, when extrapolated to older adults, explain the extremely poor outcomes and chances of survival in older adults. Another is that chemotherapy is less well tolerated with age, he told Medscape Medical News.

Dr. Attar reiterated the point made by Dr. Larsen — that the survival of AYA in this trial was higher than has been seen historically, in particular when they were treated with adult-based regimens. “We must tailor drug therapy to the specific biology of AYA disease to improve efficacy while lowering toxicity,” he explained.

Dr. Larsen has disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract CRA9508. Presented June 3, 2012.

Taking a Family History of cancer: We Can Do Better

June 25, 2012 Chemotherapy, Clinical Cases, Hematology, Therapeutics No comments , ,

June 7, 2012 (Chicago, Illinois) — Family history can be important in establishing risk for primary and secondary cancer and identifying people who might be candidates for genetic counseling and testing.

According to data presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), community oncologists are better at documenting family history in patients with breast and colorectal cancer than expected, but there is still room for improvement.

“Family history is the best criteria we have right now to identify people who are at risk for hereditary cancer syndrome and are candidates for referral and genetic testing,” said lead author Marie Wood, MD, professor of medicine, director of the familial cancer program and deputy director of hematology/oncology at the University of Vermont in Burlington.

It is critical to identify people with an above-average risk for a primary cancer and who should get additional screening, she explained during a press briefing, where highlights of the study were presented. “Cancer survivors who have a strong family history should get above-average screening for the cancer they already had and for additional cancers,” Dr. Wood said.

The researchers found that age at cancer diagnosis within the family history was documented less than half the time,” Dr. Wood noted.

“This was more commonly documented for breast cancer than for colorectal cancer patients,” she said. “When we looked at the difference between breast and colon cancer patients, it was always statistically significant.

We can and should do better.

Overall, the researchers found a high rate of documentation of cancer in first-degree relatives, albeit with a low documentation of the age at cancer diagnosis. “Family-history taking is also clearly better for breast cancer patients than colon cancer patients. We are hoping to do more with this dataset to try to figure out why that is,” Dr. Wood explained. “We can and should do better.”

The patients who underwent genetic testing received good counseling, consent documentation, and a discussion of results. “But there were low rates of referral for both counseling and testing for those who would actually benefit from it,” she said.

Family History Defines Proper Treatment

“This is a multifaceted issue and this is the first national program to help practices improve,” said Nicholas Vogelzang, MD, chair of the ASCO Cancer Communications Committee and medical director at the US Oncology Comprehensive Cancer Centers of Nevada.

Dr. Vogelzang, who moderated the press briefing and who was not involved in the study, noted that taking a good family history “is fairly laborious” and can take up to an hour to complete. This is impractical for most community oncology practices; it is hoped that the process can be expedited with the Internet.

“It is surprising how little people know about their families,” he said. It is estimated that among patients with prostate, colon, and breast cancer, about 30% are at risk for genetically transmitted disease, he explained.

In the discussion that followed Dr. Wood’s presentation, Dr. Vogelzang emphasized the practical benefits of taking a family history. He illustrated his point with the case of one of his patients — a 48-year old man with metastatic prostate cancer who was not responding well to standard treatment. After taking a thorough family history, it was revealed that his mother, sister, and aunt had all died of breast cancer.

Dr. Vogelzang said that the presentation of the man’s cancer suggested BRCA gene mutations; he had metastases in the liver and adrenals, but the cancer had not entered the skeletal system. The patient was treated with a breast cancer chemotherapy regimen and he responded beautifully.

Study Details

Previous studies have demonstrated low rates of family-history documentation and low referral rates for genetic counseling and testing, according to the researchers. The Quality Oncology Practice Initiative (QOPI) was developed by ASCO “to promote excellence in cancer care by helping practices create a culture of self-examination and improvement.” QOPI uses measurement, feedback, and improvement tools for hematology/oncology practices.

Last year, ASCO began testing new QOPI measures to evaluate the practice of family-history taking and referral for genetic counseling and testing in patients with breast cancer or colorectal cancer, explained Dr. Wood. They assessed the presence or absence of cancer in first- and second-degree relatives, age at cancer diagnosis, referral for genetic testing and counseling, and outcomes of referral.

“Our group developed pilot test questions for breast cancer and color cancer patients” using “expert consensus and participation from ASCO prevention and quality committees,” she noted.

In September and October 2011, Dr. Wood and colleagues evaluated these measures in 272 practices (6569 patients with breast cancer and 3897 with colorectal cancer). In the charts of these patients, 77.4% documented the presence or absence of cancer in first-degree relatives (breast cancer in 81.2% and colorectal cancer in 77.4%; P = < .001).

In addition, 61.5% of the charts documented the presence or absence of cancer in second-degree relatives (breast cancer in 68.9% and colorectal cancer in 57.3%; P ≤ .001).

The age at cancer diagnosis was documented for all relatives with cancer in 30.7% of the charts, and referral for counseling and/or testing was documented in 22.1% of the charts (breast cancer in 29.1% and colorectal cancer in 19.6%; P ≤ .001).

For patients with hereditary risk, defined by selected risk guidelines, the charts of 52.2% of breast cancer patients but only 26.4% of colorectal cancer patients documented referral for genetic counseling and testing. When genetic testing was performed by the practice, consent was documented 77.7% of the time and discussion of the results was documented 78.8% of the time.

The authors have disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract CRA1505. Presented June 4, 2012.

Bendamustine and Rituximab combo shines in Indolent Lymphoma

June 25, 2012 Adverse Drug Reactions, Chemotherapy, Hematology, Therapeutics No comments , , ,

June 3, 2012 (Chicago, Illinois) — New long-term results from a German trial of patients with indolent and slow-growing lymphoma confirm that a simpler 2-drug combination can be used in these patients instead of a more aggressive chemotherapy approach.

These updated results should now “be strong enough to change clinical practice,” said lead researcher Mathias Rummel, MD, PhD, professor of medicine at Justus-Liebig-University Hospital in Giessen, Germany.

The standard treatment for these more challenging types of lymphoma — which include indolent follicular, Waldenström’s, marginal zone, and mantle cell lymphoma in elderly patients — has been the R-CHOP chemotherapy regimen (rituximab [Rituxan, Genentech] plus cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone).

There has been an ongoing debate about whether such an aggressive chemotherapy combination is needed for these indolent lymphomas, Dr. Rummel noted.

The updated results from the German Study Group for Indolent Lymphoma (StiL) “clearly show” that the simpler 2-drug combination of bendamustine plus rituximab is more effective and less toxic, Dr. Rummel said.

Speaking before his presentation at the plenary session here at the 2012 Annual Meeting of the American Society of Clinical Oncology, Dr. Rummel told journalists that he expects these new results to change clinical practice, especially in the United States, where the R-CHOP regimen is still widely used.

Decades-Old Drug

Bendamustine was originally developed 50 years ago in East Germany, but there was always some skepticism about using a drug that originated from behind the Iron Curtain, he explained. It was not until reunification in 1989 that physicians in West Germany started to use the drug, Dr. Rummel said; they were impressed when it produced response rates of 90% in a phase 2 trial.

This prompted the StiL group to conduct this phase 3 trial. Previous results from this trial, reported in 2009, suggested that the 2-drug combination led to better outcomes than the R-CHOP regimen. There was some uptake of the 2-drug combination, but it was not universal, Dr. Rummel reported.

He is hopeful that the updated results will convince physicians that the 2-drug combination of bendamustine plus rituximab should be the preferred choice for first-line treatment for indolent lymphoma.

New Standard of Care

This 2-drug combination is likely to become the new standard of care, said Bruce Roth, MD, from the Department of Oncology at the Washington University School of Medicine in St. Louis, Missouri, who moderated the press conference. “It is remarkable to see better efficacy and lower toxicity,” he added.

Michael Williams, MD, from the University of Virginia Medical Center in Charlottesville, who was discussant for the abstract at the plenary session, congratulated the German group and said that the data from this trial support the use of bendamustine plus rituximab as a front-line therapy in all the types of lymphoma that were included in this trial, with the exception of marginal-zone lymphoma, for which there was no difference between the 2 treatment approaches. All the other subtypes, including low-risk and high-risk follicular lymphoma, mantle cell lymphoma, and Waldenström’s macroglobulinemia, showed a statistically significantly better progression-free survival with bendamustine plus rituximab than with R-CHOP, plus there was less toxicity with the 2-drug combination.

“I expect it to become a preferred and commonly used regimen in these disease,” he added.

Dr. Williams added 2 caveats to this: so far there are no data showing an overall survival advantage, and follow-up was just over 4 years, so there is still a need to document long-term toxic effects.

He noted that the National Comprehensive Cancer Network already includes the combination of bendamustine plus rituximab as one of the recommended front-line therapies for indolent lymphoma. He added that there has been increasing use of this combination by physicians in the United States since 2009, when Dr. Rummel presented early results from this trial.

Updated Results

The StiL trial involved 514 patients randomized to receive either bendamustine plus rituximab or the R-CHOP regimen for a maximum of 6 cycles.

The updated results come from a median follow-up of 45 months.

The primary end point of progression-free survival was twice as long with bendamustine plus rituximab as it was with R-CHOP (69.5 vs 31.2 months). “This is highly statistically significant,” Dr. Rummel emphasized. The hazard ratio was 0.58.

The overall response rate was similar with bendamustine plus rituximab and R-CHOP (92.7% vs 91.3%), but a complete response was seen in more patients on the 2-drug combination (39.8% vs 30.0%).

Overall survival did not differ between the bendamustine plus rituximab and the R-CHOP groups (43 vs 45 deaths). However, Dr. Rummel told Medscape Medical News that there was considerable crossover in the trial, and 37% of patients who progressed on R-CHOP went on to receive bendamustine plus rituximab.

“Far Better” Toxicity Profile

The toxicity profile of bendamustine plus rituximab was “by far lower,” Dr. Rummel said.

Hematologic toxicity was statistically significantly lower; leukocytopenia was seen in 12% of patients on bendamustine plus rituximab and in 38.2% on R-CHOP, and neutropenia was seen in 10.7% and 46.5%, respectively. This led to less use of granulocyte-colony stimulating factor (G-CSF) with the 2-drug combination than with R-CHOP (4% vs 20%).

“Not a single person experienced hair loss” with bendamustine plus rituximab, Dr. Rummel noted, whereas nearly all the patients on R-CHOP lost their hair.

In addition, there was less paresthesia with the 2-drug combination than with R-CHOP (18% vs 73%), and less stomatitis (16% vs 47%).

The only adverse event that was more frequent with bendamustine plus rituximab than with R-CHOP was skin reactions (42% vs 23%), but this was not statistically significant, Dr. Rummel said.

Bendamustine Available Worldwide

Bendamustine is currently available in most countries, although it is labeled for use in patients with lymphoma who are refractory to rituximab, Dr. Rummel explained. Most physicians are using it off-label in first- or second-line therapy, and are not waiting for the patient to become refractory to rituximab before using it, he said.

There is no patent protection for the drug because it was discovered so long ago, he said, but there is a data exclusivity provision that gives protection similar to a patent for the drug. It is marketed as Ribomustin in Germany and as Levact by Munidipharma Pharmaceuticals in a number of European countries, and was launched as Treanda by Cephalon in the United States.

A study analyzing the cost effectiveness of both treatments for indolent and mantle cell lymphoma from the perspective of the American healthcare payer, presented at the meeting in a poster (abstract 6553), concluded that the combination of bendamustine plus rituximab is a cost-effect alternative to R-CHOP.

Dr. Rummel reports receiving honoraria and research funding from Mundipharma and Roche Diagnostics.

2012 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract 3. Presented June 3, 2012.

Lack of awareness of Late Drug Effects in cancer survivors

June 8, 2012 Adverse Drug Reactions, Hematology, Therapeutics No comments , , , , ,

May 17, 2012 — With so many cancer patients now surviving and returning to primary care for their long-term medical care, there is an urgent need to raise awareness among primary care physicians (PCP) about the long-term adverse effects from chemotherapy. A new study shows that very few PCPs were able to correctly identify the main complications associated with 4 chemotherapies used in the 2 most common cancers — breast and colon.

“There is clearly a lot of work to be done,” said Nicholas J. Vogelzang, MD, chair of the Cancer Communications Committee at the American Society of Clinical Oncology (ASCO).

“This is a problem created by our successes,” he said; there are now more than 12 million cancer survivors living in the United States.

Results from the study, highlighted at a press briefing held in advance of the ASCO annual meeting, where they will be formally presented, “should give us pause,” Dr. Vogelzang said. The education of PCPs is essential to meet the needs of these cancers survivors, so that “the ball does not get dropped.”

The study was reported at the briefing by Larissa Nekhlyudov, MD, MPH, assistant professor of population medicine at Harvard Medical School in Boston, Massachusetts.

“While we strongly encourage patients to be aware of the chemotherapy drugs they receive and their side effects, it is vitally important that oncologists relay this information to patients’ primary care providers so that their risks can be appropriately managed throughout their lives,” she told journalists.

Large Survey

These results are the latest to come out of the Survey of Physician Attitudes Regarding the Care of Cancer Survivors (SPARCCS), which surveyed 1130 oncologists and 1072 PCPs by mail in 2009.

Previous results have shown that many PCPs feel they lack the general knowledge and confidence to care for people who have been treated with cancer.

The analysis specifically examined the long-term adverse effects of 4 widely used chemotherapies — doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan).

Most oncologists participating in the survey (62% to 97%) were able to correctly identify late adverse effects from all 4 drugs, although the researchers note that there is a need for improvement even among these specialists.

Overall, 65% of oncologists identified all 4 main late effects of the 4 chemotherapies.

In contrast, only 6% of all the PCPs were able to do so.

The most widely recognized late adverse effect was heart dysfunction with doxorubicin — identified by 55% of PCPs and 95% of oncologists.

Nearly all oncologists (97%) also recognized that peripheral neuropathy is associated with paclitaxel and with oxaliplatin, but only 26.9% and 21.8%, respectively, of PCPs also knew about this late effect.

Both sets of physicians showed the lowest awareness of the 2 late complications from cyclophosphamide therapy: premature menopause and secondary cancers. Among oncologists, 71% knew about premature menopause and 62% about the secondary malignancies, but among PCPs, only 15% and 17%, respectively, were aware of these 2 long-term complications.

Dr. Nekhlyudov emphasized the need to inform PCPs about the late effects of chemotherapy “so that they are better prepared to recognize and address these among the cancer survivors in their care.”

“At the same time, our findings underscore the need for ongoing education among all physicians who care for cancer survivors, including oncologists, about the potential late effects of treatment,” she added.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract 6008. To be presented June 2, 2012.

IDSA issues diabetic foot infection management guidelines

June 1, 2012 Diabetes, Infectious Diseases, Therapeutics No comments , , ,

Today I opened my mailbox and found there were 110+ new mails unreaded. I found this mail about Diabetes Foot and posted it here. For diabetes patient with foot we should pay attention to follows:

PS: I haven’t see diabetes patients in person and I’d like to. Pharmacists should play an important role in the antibiotics choosing.

  • A foot wound is likely to be infected if there is inflammation or purulence and/or if 2 or more of the following signs are present: redness, warmth, tenderness, pain, or swelling.
  • About half of ulcers are not infected, and these should not be treated with antibiotics.
  • Rapid, appropriate treatment of infected foot wounds is mandatory.
  • All persons with infected ulcers should receive appropriate antibiotic therapy.
  • Persons with a severe infection (accompanied by systemic signs or metabolic disturbances) should be immediately hospitalized.
  • Workup of an infected foot ulcer should include imaging of the foot to identify or rule out osteomyelitis and wound culture to identify the responsible pathogen(s) and to determine antibiotic sensitivity.
  • Although plain radiography may suffice, magnetic resonance imaging is far more sensitive and specific to diagnose osteomyelitis. This diagnosis should be confirmed by bone culture and histology.
  • Most diabetic foot infections are polymicrobial, with the most common pathogens being aerobic Gram-positive cocci (GPC), particularly staphylococci. Aerobic Gram-negative bacilli are often copathogens in chronic infections or in those arising after antibiotic treatment. Obligate anaerobes may be copathogens in ischemic or necrotic ulcers.
  • In addition to antibiotics, treatment of infected foot wounds should include surgical debridement of dead tissue, proper wound dressing, removing pressure on the wound, and improving circulation to the infected area.
  • A postdebridement specimen should be sent for aerobic and anaerobic culture.
  • Ischemia in the foot may require revascularization surgery.
  • Errors in management may include initial treatment limited to antibiotics, use of an inappropriate antibiotic, failure to provide proper wound care and surgical interventions, and failure to treat peripheral arterial disease or other underlying conditions.
  • In many acutely infected patients, empiric antibiotic therapy can narrowly target GPC. Patients at risk for infection with antibiotic-resistant organisms and those with chronic, previously treated, or severe infections usually need broader spectrum regimens.
  • The multidisciplinary team caring for patients with diabetic foot infections should include infectious diseases specialists, podiatrists, surgeons and orthopedists. Telemedicine may be useful in rural areas to increase availability of consultation with appropriate experts.
  • Patients require regular follow-up after treatment of a diabetic foot wound.
  • Clinicians and healthcare organizations should attempt to monitor and improve their procedures and outcomes in caring for diabetic foot infections.
  • These recommendations are not intended to replace clinical judgment, but to support individualized decision-making targeting each patient’s circumstances.IDSA Issues Diabetic Foot Infection Management Guidelines